Enhancer RNA facilitates NELF release from immediate early genes.

Enhancer RNA facilitates NELF release from immediate early genes.
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DOI:
10.1016/j.molcel.2014.08.023
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发表时间:
2014-10-02
期刊:
影响因子:
16
通讯作者:
Kim, Tae-Kyung
Kim, Tae-Kyung
中科院分区:
生物学1区
文献类型:
--
作者:
Schaukowitch, Katie;Joo, Jae-Yeol;Liu, Xihui;Watts, Jonathan K.;Martinez, Carlos;Kim, Tae-Kyung

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增强子RNA(eRNA)是一类由活性增强子表达的长链非编码RNA(lncRNA),其功能和作用机制尚未明确。在这里,我们表明,eRNA促进暂停RNA聚合酶II(RNAPII)的过渡到生产延长作为一个诱饵的负延伸因子(NELF)复合物诱导立即早期基因(IEGs)在神经元。eRNA在靶基因转录达到顶点之前合成,并与NELF复合物相互作用。在神经元增强子处表达的eRNA的敲低损害转录激活期间NELF从特定靶启动子的瞬时释放,与靶mRNA诱导的减少一致。增强子-启动子相互作用不受eRNA敲低的影响。相反,染色质环可能使eRNA能够在特定的启动子上局部发挥作用。我们的研究结果突出了时空调控的作用机制的eRNA在早期转录延伸。
Enhancer RNAs (eRNAs) are a class of long noncoding RNAs (lncRNA) expressed from active enhancers, whose function and action mechanism are yet to be firmly established. Here we show that eRNAs facilitate the transition of paused RNA Polymerase II (RNAPII) into productive elongation by acting as a decoy for the negative elongation factor (NELF) complex upon induction of immediate early genes (IEGs) in neurons. eRNAs are synthesized prior to the culmination of target gene transcription and interact with the NELF complex. Knockdown of eRNAs expressed at neuronal enhancers impairs transient release of NELF from the specific target promoters during transcriptional activation, coinciding with a decrease in target mRNA induction. The enhancer-promoter interaction was unaffected by eRNA knockdown. Instead chromatin looping might enable eRNAs to act locally at a specific promoter. Our findings highlight the spatiotemporally regulated action mechanism of eRNAs during early transcriptional elongation.
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